Activated and resting regulatory T cell exhaustion concurs with high levels of interleukin-22 expression in systemic sclerosis lesions.

Abstract

OBJECTIVE:

Transforming growth factor-β is considered to play a key role in the process of fibrosis in systemic sclerosis (SSc) and in the development of regulatory T cells (Treg) and pro-inflammatory Th17 T cells producing interleukin 17 (IL-17) and IL-22. The authors therefore postulated that SSc could be characterised by a marked Treg/Th17 imbalance. Previous works did not distinguish between the different subsets of Treg and the non-regulatory FoxP3(+) cells leading to inconsistent results.

METHODS:

Combined phenotypic and functional analysis of Th17 cells and FoxP3(+)CD4 T cells, discriminating activated Tregs and resting Tregs from non-regulatory FoxP3(+) T cells, in blood and skin of SSc patients.

RESULTS:

In early disease stages, there is a decreased proportion of activated Tregs. A concomitant resting Treg deficit becomes more apparent with disease progression. Active and diffuse forms of the disease are characterised by a relatively higher proportion of all FoxP3(+) subsets, including non-regulatory T cells. No peripheral or local IL-17 amplification was observed. However, the authors found significantly increased IL-22 transcription levels in SSc lesional skin, as compared with healthy skin. Cytofluorometry confirmed the existence in SSc patients and controls of a distinct subset of T cells producing IL-22 in the absence of IL-17.

CONCLUSION:

SSc pathogenesis does not appear to be linked to IL-17-, but rather to IL-22-producing cells with skin-homing potential and a concomitant quantitative Treg defect. Active and diffuse forms of the disease are associated with a FoxP3 signature. Altogether, our data depict a status of regulatory/pro-inflammatory T cell imbalance in SSc.

• Authors: Alexis Mathian, Christophe Parizot, Karim Dorgham, Salim Trad, Laurent Arnaud, Martin Larsen, Makoto Miyara, Miguel Hié, Jean-Charles Piette, Camille Frances, Hans Yssel, Zahir Amoura, Guy Gorochov
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 71 Issue 7 Pg. 1227-34 (Jul 2012) ISSN: 1468-2060 [Electronic] England
• PMID: 22696687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• FOXP3 protein, human
• Forkhead Transcription Factors
• Interleukin-17
• Interleukins

Topics

• Biomarkers (metabolism)
• Cells, Cultured
• Disease Progression
• Early Diagnosis
• Female
• Forkhead Transcription Factors (metabolism)
• Humans
• Interleukin-17 (metabolism)
• Interleukins (metabolism)
• Lymphocyte Activation
• Lymphocyte Count
• Male
• Middle Aged
• Scleroderma, Systemic (diagnosis, immunology, metabolism)
• Skin (immunology, metabolism, pathology)
• T-Lymphocytes, Regulatory (immunology, metabolism, pathology)
• Th17 Cells (immunology, metabolism, pathology)
• Interleukin-22